Effect of Fingolimod on No Evidence of Disease Activity (NEDA-4) and Safety in Young Adult Patients with Relapsing-Remitting Multiple Sclerosis (P3.277)

Abstract

OBJECTIVE: To evaluate the efficacy and safety of fingolimod 0.5mg compared to controls in young adults with relapsing-remitting MS (RRMS). BACKGROUND: NEDA-4 as a combined 4-part efficacy measure (no new or enlarging T2 lesions, no confirmed relapses, no 6-month confirmed disability progression, and annualized rate of brain atrophy of <0.4[percnt]) has been proposed as a comprehensive measure of absence of disease activity or worsening at MRI and clinical levels. We evaluated the efficacy and safety of fingolimod compared to controls by analyzing NEDA-4 and reporting on AEs in young adults. DESIGN/METHODS: Post-hoc analysis of NEDA-4 was conducted in the combined FREEDOMS and FREEDOMS II studies (2-year studies versus placebo), and in the TRANSFORMS study (1-year study versus intramuscular interferon beta-1a, IFN). NEDA-4 was analyzed in the intent-to-treat populations using a logistic regression model adjusted for treatment, age at baseline (≤30years and >30years), and treatment-by-age interaction. Proportion of patients with NEDA-4 and odds ratios (OR) versus controls were estimated for ages ≤30years and >30years. Safety in patients ≤30years was evaluated from AEs reported on fingolimod 0.5mg (N=1364) and placebo (N=966) using combined data of all controlled phase II/III studies of the fingolimod RRMS program. RESULTS: In the combined young patients (≤30years) from REEDOMS/FREEDOMS II, 24/153 (15.7[percnt]) had NEDA-4 on fingolimod compared to 4/141 (2.8[percnt]) on placebo (OR=6.37, p<0.001). In TRANSFORMS, 22/105 (21[percnt]) had NEDA-4 on fingolimod 0.5mg compared to 9/103 (8.7[percnt]) on IFN (OR=2.77, p<0.05). Similar effects were seen for patients above 30 years. The fingolimod AE profile in young adults was consistent with the known profile in the overall population. CONCLUSIONS: Young adult patients were more likely to have NEDA-4 on fingolimod compared to placebo or IFN. Efficacy and safety will be further explored in the PARADIGMS study (fingolimod versus IFN in pediatric MS), currently recruiting worldwide.

Disclosure: Dr. Ghezzi has received personal compensation for activities with Merck Serono, Novartis, Biogen Idec, Teva, Bayer Schering, Sanofi-Genzyme, Serono, and Almirall as an advisory board member and/or speaker. Dr. Karlsson has received personal compensation for activities with Novartis as an employee. Dr. Haering has received personal compensation for activities with Novartis as an employee. Dr. Gaertner has received personal compensation for activities with Novartis and Sanofi-Aventis Pharmaceuticals Inc. Dr. Chitnis has received personal compensation for activities with Biogen Idec and Alexion. Dr. Chitnis has received research support from Merck Serono and Novartis. Dr. Pohl has received personal compensation for activities with Bayer Schering, Merck Serono, and Teva Neuroscience. Dr. Putzki has received personal compensation for activities with Novartis as an employee.